eMedicine Specialties > Emergency Medicine > Rheumatology

Systemic Lupus Erythematosus: Differential Diagnoses & Workup

Author: Mark J Leber, MD, MPH, FACEP, Attending Physician and Faculty, Department of Emergency Medicine and Residency Program, Lincoln Medical and Mental Health Center
Coauthor(s): Viraj S Lakdawala, MD, Resident Physician, Department of Emergency Medicine, Lincoln Medical and Mental Health Center, Bronx, NY
Contributor Information and Disclosures

Updated: Oct 27, 2009

Differential Diagnoses

Abdominal pain
Pleuritic chest pain
Discoid skin lesions
Pneumonitis
Erythematous macules
Polyarthritis/polyarthralgia
Fatigue
Raynaud Phenomenon
Hemolytic Anemia
Renal disease
Interstitial lung disease
Renal vasculitis
Keratoconjunctivitis, Sicca
Seizures
Leukopenia
Stroke
Mucosal lesions
Thrombocytopenia
Pericarditis, Acute
Weight loss
Photo distributed rash
Pleural Effusion

Other Problems to Be Considered

Drug-induced lupus: Before making a diagnosis of systemic lupus erythematosus (SLE), ruling out drugs as the cause of the condition is important. Table 1 shows the many pharmacologic agents associated with a lupuslike syndrome. Procainamide, hydralazine, and isoniazid have been studied the best. Many patients who take these medications have positive antinuclear antibody test results and other serologic findings. Only a few have the clinical manifestations. Drug-induced lupus differs from SLE by the following features:

  • Sex ratios are nearly equal.
  • Antibodies to histones are usually found in 80-90%.
  • Nephritis and central nervous system features are not commonly present.
  • No antibodies to native DNA or hypocomplementemia are present.
  • When the drug is discontinued, the patient has resolution of clinical manifestations and reverting of abnormal laboratory values to normal.
  • Newer syndrome of drug-induced SLE has been observed with minocycline and propylthiouracil. Both drugs have a decreased frequency of antihistone antibodies and anti–double-stranded DNA antibodies, and results for antineutrophil cytoplasmic antibodies are rarely positive.

Drugs Associated With Lupus Erythematosus

Open table in new window

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Table
Definite Association
ChlorpromazineMethyldopa
HydralazineProcainamide
IsoniazidQuinidine
Possible Association
Beta-blockersMethimazole
CaptoprilNitrofurantoin
CarbamazepinePenicillamine
CimetidinePhenytoin
EthosuximidePropylthiouracil
HydrazinesSulfasalazine
LevodopaSulfonamides
LithiumTrimethadione
Unlikely Association
AllopurinolPenicillin
ChlorthalidonePhenylbutazone
Gold
salts		Reserpine
GriseofulvinStreptomycin
MethysergideTetracyclines
Oral contraceptives
Definite Association
ChlorpromazineMethyldopa
HydralazineProcainamide
IsoniazidQuinidine
Possible Association
Beta-blockersMethimazole
CaptoprilNitrofurantoin
CarbamazepinePenicillamine
CimetidinePhenytoin
EthosuximidePropylthiouracil
HydrazinesSulfasalazine
LevodopaSulfonamides
LithiumTrimethadione
Unlikely Association
AllopurinolPenicillin
ChlorthalidonePhenylbutazone
Gold
salts		Reserpine
GriseofulvinStreptomycin
MethysergideTetracyclines
Oral contraceptives

*Data from Tierney et al.21

Workup

Laboratory Studies

  • Simple laboratory tests may be helpful in making the diagnosis or in evaluating a flare. However, the diagnosis mostly depends on the historical and physical findings.
  • Rarely, autoantibody tests should be obtained in the ED, unless the workup needs to be expedited because of a diagnosis that warrants immediate diagnosis (ie, pleural effusion, renal insufficiency, myocarditis, pericarditis).
  • ECG may be warranted if the patient is experiencing chest pain, shortness of breath, or bradycardia.
  • Complete blood cell count (CBC)
    • Leukopenia, which generally is a good index for disease activity
    • Lymphopenia
    • Anemia of chronic disease (60-80%)
    • Evidence of a hemolytic anemia (10%)
    • Cytotoxic therapy (can cause anemia or leukopenia)
    • Thrombocytopenia (30-50% of cases), which may be profound secondary to antiplatelet antibodies or to antiphospholipid antibodies
  • The partial thromboplastin time (PTT) may be elevated secondary to lupus anticoagulant (antiphospholipid antibody), which is associated with thrombosis.
  • Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), or both
  • Urinalysis
    • Pyuria
    • Hematuria
    • Granular casts
    • Proteinuria
  • Chemistry, blood urea nitrogen (BUN), and creatinine levels
    • Usually not elevated at onset of disease
    • Can be useful for determining progression of renal disease
  • Joint aspiration - Can be done when patient has a monoarticular/polyarticular arthritis
  • Urine pregnancy test

Imaging Studies

  • Chest radiographs may show the following:
    • Effusion
    • Infiltrates
    • Cardiomegaly
  • Echocardiography is indicated for chest pain to rule out a pericardial effusion and any valvular pathology and to confirm any signs of pulmonary hypertension.
  • Magnetic resonance imaging (MRI) is most useful for focal neurologic deficits or cognitive dysfunction.
This axial, T2-weighted brain MRI demonstrates an...

This axial, T2-weighted brain MRI demonstrates an area of ischemia in the right periventricular white matter of a 41-year-old woman with long-standing systemic lupus erythematosus (SLE). She presented with headache and subtle cognitive impairments but no motor deficits. Faintly increased signal intensity was also seen on T1-weighted images, with a trace of enhancement following gadolinium that is too subtle to show on reproduced images. Distribution of the abnormality is consistent with occlusion of deep penetrating branches, such as may result from local vasculopathy, with no clinical or laboratory evidence of lupus anticoagulant or anticardiolipin antibody. Cardiac embolus from covert Libman-Sacks endocarditis remains less likely due to distribution.

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This axial, T2-weighted brain MRI demonstrates an...

This axial, T2-weighted brain MRI demonstrates an area of ischemia in the right periventricular white matter of a 41-year-old woman with long-standing systemic lupus erythematosus (SLE). She presented with headache and subtle cognitive impairments but no motor deficits. Faintly increased signal intensity was also seen on T1-weighted images, with a trace of enhancement following gadolinium that is too subtle to show on reproduced images. Distribution of the abnormality is consistent with occlusion of deep penetrating branches, such as may result from local vasculopathy, with no clinical or laboratory evidence of lupus anticoagulant or anticardiolipin antibody. Cardiac embolus from covert Libman-Sacks endocarditis remains less likely due to distribution.

  • Computed tomography (CT) is useful for abdominal pain and suspected pancreatitis.
  • Contrast angiography should be performed in determining the diagnosis of vasculitis. Lupus vasculitis affects medium-sized arteries and causes mesenteric or limb-threatening ischemia.

Other Tests

  • Cerebrospinal fluid (CSF) analysis is recommended when the diagnosis of CSF lupus is in question or when infection is a possible cause of symptoms.
    • High protein levels occur in 50% of patients, and pleocytosis may be found.
    • Cerebritis is associated with high protein levels.
  • Approximately 80% of patients with active CNS lupus will have an abnormal routine EEG.
    • Diffuse slow-wave activity is the pattern most typically associated with lupus, whereas focal changes are seen in patients with seizure disorder.
  • Obtain serologies in the ED only with a definitive rheumatologic consultation and follow-up.
    • Antinuclear antibody (ANA), an antibody to nucleosomal DNA-histone complexes, is more than 95% sensitive but not very specific.
    • Double-stranded DNA and aa anti-Sm (anti-Smith) antibody tests are 100% specific for lupus. Elevated anti-ds-DNA may correlate with the degree of activity of lupus and with the level of nephritis.
  • Antiphospholipid antibody
    • Antiphospholipid antibodies are only present in 30% of patients with SLE.
    • Antiphospholipid antibodies are associated with recurrent thrombosis and spontaneous abortions.
    • They are associated with normal-to-prolonged PT and prolonged plasma clot time.
    • A false-positive test result for syphilis may provide indirect evidence for the antiphospholipid antibody.
  • Complement levels (total hemolytic complement [CH50], C3, and C4)
  • Electrocardiographic changes in the assessment of chest pain may be due to pericarditis or premature coronary artery disease.

Procedures

Arthrocentesis - Cell count, viscosity, gross appearance

  • Effusion can be inflammatory or noninflammatory.
  • Cell count will reveal less than 25% PMN for noninflammatory or more than 50% for inflammatory.
  • Viscosity will be low in inflammatory or high in noninflammatory.
  • Gross appearance will be cloudy/yellow in inflammatory or straw-colored/clear in noninflammatory.

More on Systemic Lupus Erythematosus

Overview: Systemic Lupus Erythematosus
Differential Diagnoses & Workup: Systemic Lupus Erythematosus
Treatment & Medication: Systemic Lupus Erythematosus
Follow-up: Systemic Lupus Erythematosus
Multimedia: Systemic Lupus Erythematosus
References
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Further Reading

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Contributor Information and Disclosures

Author

Mark J Leber, MD, MPH, FACEP, Attending Physician and Faculty, Department of Emergency Medicine and Residency Program, Lincoln Medical and Mental Health Center
Mark J Leber, MD, MPH, FACEP is a member of the following medical societies: American College of Emergency Physicians and American College of Physicians
Disclosure: Nothing to disclose.

Coauthor(s)

Viraj S Lakdawala, MD, Resident Physician, Department of Emergency Medicine, Lincoln Medical and Mental Health Center, Bronx, NY
Viraj S Lakdawala, MD is a member of the following medical societies: American Academy of Emergency Medicine and American College of Emergency Physicians
Disclosure: Nothing to disclose.

Medical Editor

Richard S Krause, MD, Senior Faculty, Department of Emergency Medicine, State University of New York at Buffalo School of Medicine
Richard S Krause, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Gino A Farina, MD, Program Director, Associate Professor of Clinical Emergency Medicine, Department of Emergency Medicine, Long Island Jewish Medical Center, Albert Einstein College of Medicine
Gino A Farina, MD is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Rick Kulkarni, MD, Assistant Professor of Surgery, Section of Emergency Medicine, Yale-New Haven Hospital
Rick Kulkarni, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Emergency Physicians, American Medical Association, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: WebMD Salary Employment

 
 
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